scholarly journals Origin of the plant Tm-1-like gene via two independent horizontal transfer events and one gene fusion event

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Zefeng Yang ◽  
Li Liu ◽  
Huimin Fang ◽  
Pengcheng Li ◽  
Shuhui Xu ◽  
...  
Keyword(s):  
Horizontal Transfer ◽  
Gene Fusion ◽  
Fusion Event ◽  
Gene Fusion Event

scholarly journals A functionally conserved STORR gene fusion in Papaver species that diverged 16.8 million years ago

2021 ◽  
Author(s):  
Theresa Catania ◽  
Yi Li ◽  
Thilo Winzer ◽  
David Harvey ◽  
Fergus Meade ◽  
...  
Keyword(s):  
Gene Fusion ◽  
Gene Tree ◽  
Genomic Analysis ◽  
Duplication Event ◽  
Opium Poppy ◽  
Fusion Event ◽  
Genome Duplication Event ◽  
Benzylisoquinoline Alkaloid ◽  
Gene Fusion Event ◽  
Important Exception

The STORR gene fusion event is considered a key step in the evolution of benzylisoquinoline alkaloid (BIA) metabolism in opium poppy as the resulting bi-modular protein performs the isomerization of (S)- to (R)- reticuline which is required for morphinan biosynthesis. Our previous analysis of the opium poppy genome suggested the STORR gene fusion event occurred before a whole genome duplication event 7.2 million years ago. Here we use a combination of phylogenetic, transcriptomic, metabolomic, biochemical and genomic analysis to investigate the origin of the STORR gene fusion across the Papaveraceae family. The pro-morphinan/morphinan subclass of BIAs was present in a subset of 10 Papaver species including P. somniferum (opium poppy) and this correlated with the presence of the STORR gene fusion with one important exception. P. californicum does not produce morphinans but it does contain a STORR gene fusion that epimerizes (S)- to (R)- reticuline when heterologously expressed in yeast. The high similarity of the amino acid sequence linking the two modules of STORR along with phylogenetic gene tree analysis strongly suggests the gene fusion occurred only once and between 17-25 million years ago before the separation of P. californicum from the other Papaver species. We discovered that the most abundant BIA in P. californicum is (R)- glaucine, a member of the aporphine subclass of BIAs. Only the (S) isomer of this compound has previously been reported from nature. These results lead us to conclude that the function of the STORR gene fusion is not exclusive to morphinan production in the Papaveraceae.

scholarly journals Pan-genomic characterization of high-risk pediatric papillary thyroid carcinoma

2021 ◽  
Vol 28 (5) ◽  
pp. 337-351
Author(s):  
Adam Stenman ◽  
Samuel Backman ◽  
Klara Johansson ◽  
Johan O Paulsson ◽  
Peter Stålberg ◽  
...  
Keyword(s):  
High Risk ◽  
Single Case ◽  
Papillary Thyroid ◽  
Fusion Event ◽  
Term Outcome ◽  
Primary Tumors ◽  
Long Term Outcome ◽  
Regulatory Pathways ◽  
Genomic Landscape ◽  
Gene Fusion Event

Pediatric papillary thyroid carcinomas (pPTCs) are often indolent tumors with excellent long-term outcome, although subsets of cases are clinically troublesome and recur. Although it is generally thought to exhibit similar molecular aberrancies as their counterpart tumors in adults, the pan-genomic landscape of clinically aggressive pPTCs has not been previously described. In this study, five pairs of primary and synchronously metastatic pPTC from patients with high-risk phenotypes were characterized using parallel whole-genome and -transcriptome sequencing. Primary tumors and their metastatic components displayed an exceedingly low number of coding somatic mutations and gross chromosomal alterations overall, with surprisingly few shared mutational events. Two cases exhibited one established gene fusion event each (SQSTM1-NTRK3 and NCOA4-RET) in both primary and metastatic tissues, and one case each was positive for a BRAF V600E mutation and a germline truncating CHEK2 mutation, respectively. One single case was without apparent driver events and was considered as a genetic orphan. Non-coding mutations in cancer-associated regions were generally not present. By expressional analyses, fusion-driven primary and metastatic pPTC clustered separately from the mutation-driven cases and the sole genetic orphan. We conclude that pPTCs are genetically indolent tumors with exceedingly stable genomes. Several mutations found exclusively in the metastatic samples which may represent novel genetic events that drive the metastatic behavior, and the differences in mutational compositions suggest early clonal divergence between primary tumors and metastases. Moreover, an overrepresentation of mutational and expressional dysregulation of immune regulatory pathways was noted among fusion-positive pPTC metastases, suggesting that these tumors might facilitate spread through immune evasive mechanisms.

scholarly journals Detection of a Novel, and Likely Ancestral, Tn916-Like Element from a Human Saliva Metagenomic Library

Genes ◽  
2020 ◽  
Vol 11 (5) ◽  
pp. 548
Author(s):  
Liam J. Reynolds ◽  
Muna F. Anjum ◽  
Adam P. Roberts
Keyword(s):  
Resistance Genes ◽  
Metagenomic Library ◽  
Tetracycline Resistance ◽  
Human Saliva ◽  
Fusion Event ◽  
Tetracycline Resistance Genes ◽  
Antimicrobial Resistance Genes ◽  
Genes Encoding ◽  
Gene Fusion Event ◽  
Metagenomic Approach

Tn916 is a conjugative transposon (CTn) and the first reported and most well characterised of the Tn916/Tn1545 family of CTns. Tn916-like elements have a characteristic modular structure and different members of this family have been identified based on similarities and variations in these modules. In addition to carrying genes encoding proteins required for their conjugation, Tn916-like elements also carry accessory, antimicrobial resistance genes; most commonly the tetracycline resistance gene, tet(M). Our study aimed to identify and characterise tetracycline resistance genes from the human saliva metagenome using a functional metagenomic approach. We identified a tetracycline-resistant clone, TT31, the sequencing of which revealed it to encode both tet(M) and tet(L). Comparison of the TT31 sequence with the accessory, regulation, and recombination modules of other Tn916-like elements indicated that a partial Tn916-like element encoding a truncated orf9 was cloned in TT31. Analysis indicated that a previous insertion within the truncated orf9 created the full length orf9 found in most Tn916-like transposons; demonstrating that orf9 is, in fact, the result of a gene fusion event. Thus, we hypothesise that the Tn916-like element cloned in TT31 likely represents an ancestral Tn916.

154 Genomic Landscape of Radiation-Induced Meningiomas

Neurosurgery ◽  
2017 ◽  
Vol 64 (CN_suppl_1) ◽  
pp. 238-238
Author(s):  
Suganth Suppiah ◽  
Sameer Aghinotri ◽  
Pete Tonge ◽  
Yasin Mamatjan ◽  
Kenneth D Aldape ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Rna Sequencing ◽  
Genomic Analysis ◽  
Fold Increase ◽  
Sequencing Data ◽  
Dna Breaks ◽  
Fusion Event ◽  
Chromosome 1P ◽  
Gene Fusion Event ◽  
Radiation Induced

Abstract INTRODUCTION Majority of pediatric cancers require the irradiation of the central nervous system (CNS), and as more patients survive into adulthood from improved oncological therapy the sequelae of brain radiation are increasing in prevalence. Radiation-induced meningiomas (RIMs), one such secondary effect, demonstrate a clinically more aggressive behaviour than sporadic meningiomas (SMs). We aimed to describe the genomic mutational landscape of RIMs METHODS We analyzed a principal cohort of 18 RIMs, with 31 RIMs overall, from patients who received childhood radiation therapy and 30 SMs, as a comparator population. We performed a multiplatform integrative genomic analysis; including methylation, whole exome and RNA sequencing. RESULTS >RIMs exhibited a five-fold increase in copy number alterations, commonly the loss of chromosome 1p (17/18 RIMs) and 22q (17/18 RIMs), which was significantly more than observed in sporadic meningiomas. Furthermore, RNA sequencing data revealed an NF2 gene fusion event in 35.3% of RIMs In all 6 cases, there was a complete NF2 exon spliced into a complete exon of a reciprocal gene, suggesting that the breakpoints of genomic rearrangement are intronic. All tumours with the NF2 fusion also possessed monosomy of chromosome 22q, rendering the cells with homozygous disruption of NF2. Clinically, RIMs with the NF2 fusion exhibited ill-defined borders and a tendency to develop in anatomic frontal location. The NF2 fusion RIMs, also, had a significantly faster growth rate compared to non-fusion RIMS (P < 0.05). Also, targeted sequencing panel confirmed that RIMs had fewer nonsynonymous NF2 mutations (6.5% vs. 30% in SM) and absence of mutations in TRAF7, SMO, KLF4, PIK3CA and AKT1, genes traditionally involved in SMs. CONCLUSION Our study demonstrates that RIMs have distinct genomic drivers of oncogenesis as compared to SMs, specifically NF2 inactivation through fusion event. Radiation therapy possibly triggers genomic structural rearrangements through error-prone repair of double-stranded DNA breaks.

scholarly journals Mapping Functional Associations in the Entire Genome ofDrosophila melanogasterUsing Fusion Analysis

2003 ◽  
Vol 4 (3) ◽  
pp. 337-341 ◽  
Author(s):  
Ioannis Iliopoulos ◽  
Anton J. Enright ◽  
Patrick Poullet ◽  
Christos A. Ouzounis
Keyword(s):  
Gene Fusion ◽  
Sequence Similarity ◽  
Developmental Pathways ◽  
Fusion Event ◽  
Entire Genome ◽  
Additional Information ◽  
Low Degree ◽  
Associated Proteins ◽  
Fusion Analysis ◽  
Additional Constraints

We have previously shown that the detection of gene fusion events can contribute towards the elucidation of functional associations of proteins within entire genomes. Here we have analysed the entire genome ofDrosophila melanogasterusing fusion analysis and two additional constraints that improve the reliability of the predictions, viz. low sequence similarity and low degree of paralogy of the component proteins involved in a fusion event. Imposing these constraints, the total number of unique component pairs is reduced from 18 654 to a mere 220 cases, which are expected to represent some of the most reliably detected functionally associated proteins. Using additional information from sequence databases, we have been able to detect pairs of functionally associated proteins with important functions in cellular and developmental pathways, such as spermatogenesis and programmed cell death.

Acquisition of genome-wide copy number alterations in monozygotic twins with acute lymphoblastic leukemia

Blood ◽  
2010 ◽  
Vol 115 (17) ◽  
pp. 3553-3558 ◽  
Author(s):  
Caroline M. Bateman ◽  
Susan M. Colman ◽  
Tracy Chaplin ◽  
Bryan D. Young ◽  
Tim O. Eden ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Copy Number ◽  
Lymphoblastic Leukemia ◽  
Monozygotic Twins ◽  
Cell Receptor ◽  
Copy Number Alterations ◽  
Fusion Event ◽  
Evolutionary Trajectory ◽  
Genome Wide ◽  
Gene Fusion Event

Abstract Chimeric fusion genes are highly prevalent in childhood acute lymphoblastic leukemia (ALL) and are mostly prenatal, early genetic events in the evolutionary trajectory of this cancer. ETV6-RUNX1–positive ALL also has multiple (∼ 6 per case) copy number alterations (CNAs) as revealed by genome-wide single-nucleotide polymorphism arrays. Recurrent CNAs are probably “driver” events contributing critically to clonal diversification and selection, but at diagnosis, their developmental timing is “buried” in the leukemia's covert natural history. This conundrum can be resolved with twin pairs. We identified and compared CNAs in 5 pairs of monozygotic twins with concordant ETV6-RUNX1–positive ALL and 1 pair discordant for ETV6-RUNX1 positive ALL. We compared, within each pair, CNAs classified as potential “driver” or “passenger” mutations based upon recurrency and, where known, gene function. An average of 5.1 (range 3-11) CNAs (excluding immunoglobulin/T-cell receptor alterations) were identified per case. All “driver” CNAs (total of 32) were distinct within each of the 5 twin pairs with concordant ALL. “Driver” CNAs in another twin with ALL were all absent in the shared ETV6-RUNX1–positive preleukemic clone of her healthy co-twin. These data place all “driver” CNAs secondary to the prenatal gene fusion event and most probably postnatal in the sequential, molecular pathogenesis of ALL.

scholarly journals Gene Fusion Detection By RNA-Seq in Acute Myeloid Leukemia (AML)

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4655-4655
Author(s):  
Paul Kerbs ◽  
Aarif Mohamed Nazeer Batcha ◽  
Sebastian Vosberg ◽  
Dirk Metzler ◽  
Tobias Herold ◽  
...  
Keyword(s):  
Chromosomal Aberrations ◽  
Gene Fusion ◽  
Fusion Transcript ◽  
Clinical Diagnostics ◽  
Fusion Genes ◽  
Rna Seq ◽  
Fusion Event ◽  
Routine Diagnostics ◽  
Partner Gene ◽  
Fusion Detection

Accurate and complete genetic classification of AML is crucial for the prediction of clinical outcome and treatment stratification. Deciphering the spectrum of genetic abnormalities by polymerase chain reaction (PCR), karyotyping and fluorescence in situ hybridization (FISH) in routine diagnostics is the current gold standard, however, fusion genes might potentially be missed by these assays. Recently, several methods have been developed to improve the detection of gene fusion transcripts based on RNA sequencing data, providing robust results. To test the detection power and assess the applicability of RNA-Seq based methods in clinical diagnostics we applied two different algorithms, namely FusionCatcher (Nicorici D et al., bioRxiv, 2014) and Arriba (Uhrig S et al., DKFZ, https://github.com/suhrig/arriba), to the transcriptomes of 895 well-characterized AML samples from three independently sequenced cohorts: AMLCG (Herold T et al., Haematologica, 2018, n=261), DKTK (Greif PA et al., Clin Cancer Res, 2018 and unpublished data, n=166), BeatAML (Tyner JW et al., Nature 2018, n=468) and publicly available healthy control samples (SRA studies: SRP018028, SRP047126, SRP050146, SRP105369, SRP115911, SRP133442, n=38). According to karyotyping, 31% (277/895) of samples harbored chromosomal aberrations putatively causing gene fusions (i.e. translocations, interstitial deletions, duplications, inversions, insertions). Analyses by FISH and/or PCR confirmed these rearrangements in 51.3% (142/277) of samples, whereas fusion detection by the means of RNA-Seq showed evidence for fusion genes corresponding to these rearrangements in 60.3% (167/277) of samples. Chromosomal aberrations, identified by karyotyping, which are known to result in clinically relevant fusions (e.g. RUNX1-RUNX1T1, KMT2A fusions) were confirmed by FISH/PCR (AMLCG: n=27/27, DKTK: n=21/21, BeatAML: n=54/57) and RNA-Seq based methods (AMLCG: n=17/27, DKTK: n=21/21, BeatAML: n=56/57) in most of the cases. Of note, the AMLCG cohort was sequenced using the SENSE mRNA Library Prep Kit from Lexogen which seems to be not optimal for fusion detection. Furthermore, 19 samples (AMLCG: n=12, DKTK: n=4, BeatAML: n=3) were found to harbor known pathogenic fusions, described in previous studies, which were not reported by routine diagnostics: NUP98-NSD1 (n=11); CBFB-MYH11, RUNX1-RUNX1T1 and DEK-NUP214 (n=2 each); RUNX1-CBFA2T2 and RUNX1-CBFA2T3 (n=1 each). Reanalysis of six of these samples by PCR confirmed three fusions which were initially missed by routine diagnostics. In general, the amount of reported fusion events by RNA-Seq is high (on average 69 and 39 per sample as detected by FusionCatcher and Arriba respectively), even after applying the built-in filters, indicating a high false positive rate. To robustly identify putative novel fusions, we developed a filtering pipeline and incorporated two new filtering steps. The promiscuity score (PS) of a fusion measures the amount of further distinct fusion partners which were detected in the respective cohort for the 5' and 3' gene. The fusion transcript score (FTS) measures the relative abundance of a fusion transcript to its 5' and 3' partner gene. PS and FTS of known, clinically relevant fusions confirmed by FISH/PCR were used to define cut-offs. To further maximize specificity while maintaining sensitivity, we excluded fusion events which we detected in publicly available healthy samples and subsequently filtered for overlapping calls from FusionCatcher and Arriba (Fig. 1A). Additionally, we obtained further evidence for a fusion event by an elevated transcription of the 3' fusion partner. In case of a fusion event, the transcription of the 3' partner gene likely gets under the control of the promoter of the 5' partner gene. This results in an elevated transcription of genes which are otherwise transcribed at low levels (Fig. 1B-C). Thus, we identified five putatively novel recurrent fusion genes which were detected in two cohorts independently: NRIP1-MIR99AHG, LATS2-ZMYM2, ATP11A-ING1, MBP-SLC66A2, PRDM16-SKI (Fig. 1D-F). Although these events were called with high evidence, we aim at independent validation by complementary methods. In our study, we have not only demonstrated that the application of RNA-Seq to the detection of fusion genes is a valuable complement to diagnostic routine but also has the potential to discover novel putatively pathogenic fusions. Disclosures No relevant conflicts of interest to declare.

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